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PubMed1996

Consequences of alteration in capillary permeability.

In this review paper, three aspects related to alteration in capillary permeability, based on a series of recent observations from this laboratory, are examined. Firstly, the determinants of capillary extravasation, which include pre- and post-capillary resistances in different microcirculation networks, as well as endothelial permeability per se, are described with particular reference to the heterogeneous character of both regulatory components, reported by this and other groups. Secondly, the endothelium-interstitium relationship, responsible in part for the maintenance of the interstitial compartment physicochemical characteristics, is introduced as an important factor in regulating the traffic of vital nutrients delivered to the cell mass, and the removal of waste products from the cellular compartment to the microcirculation, for ultimate excretion. Examined in this manner, it appears that modulation of capillary permeability is essential for the maintenance of cellular life, yet the neurohumoral mechanisms involved in the control of microcirculation networks are just starting to be identified. A number of morbid conditions characterized by multiorgan involvement exhibit a common pathophysiological denominator which involves endothelium-interstitium relationships, as illustrated in experimental animal models of arterial hypertension, diabetes mellitus, heart failure, and degenerative renal diseases. Enhanced capillary permeability associated with local interstitial edema in specific organs, such as the heart and the kidney, in arterial hypertension and diabetes mellitus, as well as decreased permeability in peripheral tissues, such as the skeletal muscle and the skin, in congenital cardiomyopathy, have been documented. It is likely that alteration in the characteristics of interstitial matrix composition contributes to target organ damage in these examples of systemic disorders from different etiologies. Thirdly, the recent identification of autocoids and hormones involved in the direct and indirect control of capillary permeability has led to the development of pharmacological tools capable of modulating pre- and post-capillary vascular tonus, as well as endothelial permeability. Angiotensin II antagonism, bradykinin B1-receptor inhibition, and modulation of eicosanoid production, in particular thromboxane A2, are associated in some of the above-described disorders, with normalization of capillary permeability defects, and occasionally with improvement in organ function. The eventual development of agents capable of directly controlling the physicochemical characteristics of the interstitial matrix should be of interest, not only for preventing the development of irreversible matrix structural alterations but also for facilitating the traffic of metabolites between capillaries and the cell mass of vital organs.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2002

PKQuest: capillary permeability limitation and plasma protein binding - application to human inulin, dicloxacillin and ceftriaxone pharmacokinetics.

BACKGROUND: It is generally assumed that the tissue exchange of antibiotics is flow limited (complete equilibration between the capillary and the tissue water). This assumption may not be valid if there is a large amount of plasma protein binding because the effective capillary permeability depends on the product of the intrinsic capillary permeability (PS) and the fraction of solute that is free in the blood (fwB). PKQuest, a new generic physiologically based pharmacokinetic software routine (PBPK), provides a novel approach to modeling capillary permeability in which the only adjustable parameter is the PS of muscle. METHODS: All the results were obtained by applying PKQuest to previously published human pharmacokinetic data. RESULTS: The PKQuest analysis suggests that the highly protein bound antibiotics dicloxacillin and ceftriaxone have a significant capillary permeability limitation. The human muscle capillary PS of inulin, dicloxacillin and ceftriaxone was 0.6, 13 and 6 ml/min/100 gm, respectively. The ceftriaxone protein binding is non-linear, saturating at high plasma concentrations. The experimental ceftriaxone data over a wide range of intravenous inputs (0.15 to 3 gms) was well described by PKQuest. PKQuest is the first PBPK that includes both permeability limitation and non-linear binding. CONCLUSIONS: Because of their high degree of plasma protein binding, dicloxacillin and ceftriaxone appear to have a diffusion limited exchange rate between the blood and tissue and are not flow limited as had been previously assumed. PKQuest and all the examples are freely available at http:\\www.pkquest.com.

Adult↗
PubMed2005

The induction of vascular endothelial growth factor by ultrafine carbon black contributes to the increase of alveolar-capillary permeability.

Ultrafine carbon black (ufCB) can cause proinflammatory response and increase alveolar-capillary permeability. However, the mechanism underlying the increased permeability is not well characterized. Vascular endothelial growth factor (VEGF) is originally recognized as a vascular permeability factor. Oxidative stress generated by hydrogen peroxide (H2O2) stimulates VEGF gene expression. The purpose of this study was to explore the role of VEGF in ufCB-induced alveolar-capillary permeability. Intratracheal instillation of 200 microg ufCB in mice caused a significant and sustained increase of total proteins in bronchoalveolar lavage (BAL) fluid, with the maximal increase at 21 hr postinstillation. The influx of neutrophils did not significantly increase until 16 hr. It reached the highest level at 21 hr and returned to the basal level by 42 hr. Tumor necrosis factor-alpha was significantly elevated only at 4 hr. ufCB induced significant increases of VEGF in BAL fluid throughout the study period, with the peak increase at 16 hr. The nonsecreted isoform VEGF188 was not altered after 16 hr of exposure to ufCB. Moreover, there was a strong correlation between VEGF and total proteins in BAL fluid (R2 = 0.7352, p < 0.01). In vivo study supported the role of reactive oxygen species (ROSs) in ufCB-induced VEGF release and protein leakage. The involvement of ROSs was strengthened by the fact that interventions with N-acetylcysteine prevented ufCB-induced generation of ROSs and VEGF in vitro. Our study for the first time demonstrates that ufCB induces the production of VEGF, which is associated with the increase of alveolar-capillary permeability. The induction of VEGF by ufCB acts through an ROS-dependent pathway.

Acetylcysteine↗
PubMed1994

A junction-orifice-fiber entrance layer model for capillary permeability: application to frog mesenteric capillaries.

The recent serial section electron microscopic studies by Adamson and Michel (1993) on microves gels of frog mesentery have revealed that the large pores in the junction strand of the interendothelial cleft are widely separated 150 nm wide orifice-like breaks whose gap height 20 nm is the same as the wide part of the cleft. In this paper a modified version of the model in Weinbaum et al. (1992) is first developed in which this orifice structure is explored in combination with a random or ordered fiber matrix layer that is at the luminal surface and/or occupies a fraction of the wide part of the cleft. This basic orifice model predicts that for the measured Lp to be achieved the fiber layer must be confined to a relatively narrow region at the entrance to the cleft where it serves as the primary molecular filter. The model provides a much better fit of the permeability P for intermediate size solutes between 1 and 2 nm radius than the previous model in Weinbaum et al., where the junction strand breaks were treated as finite depth circular or rectangular pores, but like the previous model significantly underestimates P for small ions. However, it is shown that if a small frequent pore of 1.5 nm radius with characteristic spacing comparable to the diameter of the junction proteins or a continuous narrow slit of approximately 1.5 to 2.3 nm gap height is also present in the continuous part of the junction strand, small ion permeability can also be satisfied. The 1.5 nm radius pore does not significantly change Lp, whereas the continuous narrow slit provides a contribution to Lp that is comparable to, or in the case of the 2.3 nm slit greater than, the widely spaced 150 nm orifices. Thus, for the narrow slit the contribution to Lp from the orifices can be as low as 1.0 x 10(-7) cm/s/cm H2O and it is also possible to satisfy the 2.5 fold increase in permeability that occurs when the matrix is enzymatically removed from the luminal side of the cleft, Adamson (1990). The likelihood of each of these cleft structures is discussed.

Animals↗
PubMed1976

Capillary permeability in adipose tissue.

A method for measurement of capillary permeability using external registration of gamma emitting isotopes after close arterial bolus injection was applied to the isolated inguinal fat pad in slightly fasting rabbits. An average extraction of 26 per cent for 51Cr-EDTA was found at a plasma flow of about 7 ml/100 g-min. This corresponds to a capillary diffusion capacity of 2.0 ml/100 g-min which is half the value reported for vasodilated skeletal muscle having approximately twice as great capillary surface area. Thus, adipose tissue has about the same capillary permeability during slight metabolic activation as vasodilated skeletal muscle.

Adipose Tissue↗
PubMed2000

Simvastatin, capillary permeability, and acetylcholine-mediated vasomotion in atherosclerotic, hypercholesterolemic men.

OBJECTIVES: The aim of this study was to test the effect of high-dose simvastatin therapy on vascular permeability, a key variable in the atherogenic process, and endothelial-mediated vasodilator responses in patients with hypercholesterolemic atherosclerosis. METHODS: The transcapillary albumin escape rate (TERalb, the 1-hour decline rate of intravenous 125I-albumin, a measure of macromolecular permeability of capillary endothelium) and forearm vasodilatation (venous plethysmography) to intraarterial acetylcholine and sodium nitroprusside (7.5, 15, 30 microg/min and 0.8, 1.6, and 3.2 microg/min respectively, 5 minutes at each rate) to account for endothelium-dependent and independent mechanisms, were measured at baseline and after 1-month simvastatin (40 mg once daily) in 16 hypercholesterolemic (low-density lipoprotein cholesterol >130 mg/dL), atherosclerotic men. Thirteen healthy, untreated subjects were the controls. RESULTS: Baseline TERalb was higher and responsiveness to both acetylcholine and sodium nitroprusside was depressed in patients compared with controls. One-month high-dose simvastatin reduced low-density lipoprotein cholesterol by 39%, normalized TERalb, and improved local vasomotor responses to acetylcholine, without modifying those to sodium nitroprusside. Changes in TERalb and acetylcholine-mediated vasodilatation were dissociated and unrelated to lipid modifications. CONCLUSIONS: Low-density lipoprotein cholesterol reduction through 1 month of high-dose simvastatin normalized the exaggerated transvascular albumin leakage of patients with hypercholesterolemic atherosclerosis, perhaps by restoring an exaggerated endothelial permeability, apparently through mechanisms independent of circulating lipids. Improvements in acetylcholine-mediated vasomotion were also evident, but were dissociated from TERalb, demonstrating a heterogeneous behavior of the 2 indices of endothelial function in response to high-dose statin treatment.

Acetylcholine↗
PubMed2005

Evaluation of alveolo-capillary permeability in thyrotoxicosis using Tc-99m DTPA aerosol scintigraphy.

Surfactant secreted from type II pneumocytes plays an important role in alveolo-capillary permeability. In thyrotoxicosis, high levels of T3 receptors detected at these cells might affect the alveolo-capillary permeability due to increased serum thyroid hormone levels. The results by CO-diffusion capacity measurement in thyrotoxicosis are conflicting. Changes in alveolo-capillary membrane permeability resulting from thyrotoxicosis are not well established yet. This prompted us to investigate the alveolo-capillary permeability in thyrotoxic patients in comparison with CO-diffusing capacity. For this aim twenty-two non-smoking thyrotoxic patients (before treatment) and fifteen healthy voluntary controls underwent 99mTc-DTPA aerosol scintigraphy. CO-diffusing and pulmonary function tests were performed in all subjects. After ventilation of radiotracer through a nebulizer for 15 minutes, 30 dynamic images (1 frame/minute) were taken from both lungs. ROI's were drawn over both lung areas, and the time-activity curves were generated. Then clearance half time (CT1/2) for radioaerosol was obtained. CT1/2 of thyrotoxic patients did not differ from that of the controls: 77.9 +/- 25.9 min vs. 79.4 +/- 22.3 min; p > 0.05. Similar result was found for CO-diffusion parameters. Also there was no significant correlation between CT1/2 and CO-diffusion parameters. We concluded that in patients with thyrotoxicosis, the alveolo-capillary permeability is unaffected. Further experimental research is needed to establish the possible effects of thyroid hormones on alveolo-capillary membrane.

Adolescent↗
PubMed1992

Capillary permeability of 99mTc-DTPA and blood flow rate in the human myocardium determined by intracoronary bolus injection and residue detection.

The aims of the present study were to quantitate blood flow rate and capillary permeability of 99mTc-DTPA in the human myocardium and to assess whether capillary permeability is influenced by the presence of small degree atherosclerotic lesions. Myocardial blood flow rate and capillary permeability of 99mTc-DTPA were quantitated during coronary angiography by the single injection, residue detection method. Eighteen patients undergoing a diagnostic coronary angiography because of uncharacteristic chest pain were studied. In 12 patients with angiographically normal epicardial coronary arteries, a mean value of the capillary permeability-surface area (PS) product of 54.0 ml.(100 g.min)-1 (SD 13.0) was determined from a capillary extraction of 55.0% (SD 9.4%) and a regional myocardial plasma flow rate of 74.6 ml.(100 g.min)-1 (SD 6.3) equivalent with a regional myocardial blood flow rate of 121.7 ml.(100 g.min)-1 (SD 13.0). Similar values of blood flow rate, capillary extraction fraction and the PS product were determined in 6 patients with localized coronary atheroma without hemodynamically significant coronary artery stenosis (25-50% luminal narrowing). The values for the regional myocardial blood flow rate in the human heart are in accordance with values obtained by other methods, and the PS product of 99mTc-DTPA is similar to results obtained in canine hearts. Localized coronary atheroma leading to insignificant coronary artery stenosis does not produce any measurable dysfunction of the coronary microcirculation, in terms of capillary permeability and blood flow rate, during resting conditions.

Adult↗
PubMed2004

The effects of hydroxyethyl starch on lung capillary permeability in endotoxic rats and possible mechanisms.

UNLABELLED: In this study we examined the effects of hydroxyethyl starch (HES 200/0.5) on lung capillary permeability in endotoxic rats and explored the possible mechanisms. Male Wistar rats were randomly divided into seven groups treated with saline, lipopolysaccharide (LPS; 6 mg/kg), LPS plus HES (3.75, 7.5, 15, or 30 mL/kg), or HES (30 mL/kg) alone for 4 or 2 h. Lung capillary permeability, lung neutrophil accumulation, expression of CD11b on the blood neutrophil cell surface, lung cytokine-induced neutrophil chemoattractant protein level, and nuclear factor kappa B (NF-kappaB) activation in blood neutrophils and lungs were measured. HES at doses of 3.75 and 7.5 mL/kg significantly reduced LPS-induced increases of lung capillary permeability. HES was found to inhibit lung neutrophil accumulation, cytokine-induced neutrophil chemoattractant protein, and NF-kappaB activation in parallel and to inhibit CD11b expression in a dose-dependent manner. These findings demonstrate that HES has beneficial effects on capillary leak in acute lung injury and that the mechanisms underlying this action involve an antiinflammatory effect of HES, including inhibition of NF-kappaB activation. IMPLICATIONS: A randomized, controlled laboratory experiment indicated that hydroxyethyl starch (HES) could reduce increased lung capillary permeability in endotoxemia. This effect may be due to an antiinflammatory effect of HES.

Animals↗
PubMed1994

Capillary permeability in fibromyalgia.

OBJECTIVE: To examine capillary permeability in fibromyalgia (FMS) we studied the nailfold capillaries of 13 unselected patients with FMS and 9 healthy controls using dynamic fluorescence videomicroscopy. METHODS: The transcapillary permeability of a 20% solution of sodium fluorescein injected into an antecubital vein was assessed by videodensitometric analysis. The pericapillary and interstitial fluorescent light intensities (FLI) were calculated at different sites on a transverse axis crossing the selected capillary. RESULTS: Fluorescence videomicroscopy revealed no abnormalities in the pattern of dye distribution around the nailfold capillaries in the patient group. Videodensitometric analysis showed a trend to an increased early transcapillary diffusion in patients with FMS, but the difference was only significant at 3 s from the first appearance of the dye (p < 0.05). From 10 s to 1 min after the dye's appearance, the mean FLI in the patients equalled that of the controls. The patients with FMS showed an earlier but lower FLI peak. Moreover, the FLI were significantly lower in the patients than in the controls from 5 to 30 min after the dye appearance in all of the sites of the densitometric analysis (p < 0.05). Thirty min after the first appearance of the dye, the FLI was reduced by more than 50% in the patient group compared to the controls. CONCLUSION: Our results indicate that transcapillary permeability and the interstitial persistence of the tracer in FMS are significantly reduced compared to controls. This difference may be caused by the abnormal microvascular dynamics induced by low capillary flow and/or capillary bed hypotension.

Adult↗
PubMed2002

[Effects of salicylate on the capillary permeability of inner ear in guinea pigs].

OBJECTIVE: To further understand the mechanism of salicylate ototoxicity. METHOD: The capillary permeability of inner ear was compared between the normal group and the salicylate ototoxicity group traced with lanthanum by electron microscopy. RESULT: The normal inner/outer spiral vessels of basilar membrane, strial blood vessels had no permeability, whereas the capillaries of endolymphatic sac showed a certain permeability. In salicylate ototoxicity group, the permeability of the capillaries mentioned above increased significantly. CONCLUSION: Salicylate may increase the capillary permeability in inner ear, which may participate in the mechanism of the salicylate ototoxicity.

Animals↗
PubMed1988

Muscle capillary permeability for [14C]inulin and [51Cr]EDTA in human forearm.

Capillary permeability of [14C]inulin and [51Cr]EDTA was examined in human forearm in five healthy, subjects by indicator diffusion technique. Injections of, initially [125I]albumin and [14C]inulin, and after 30 min resting, of [125I]albumin and [51Cr]EDTA, were given in a brachial artery. During light exercise of the forearm, blood was sampled in 2-s periods from a deep cubital vein primarily draining muscles. The plasma flow rate, calculated as the dose of [125I]albumin in the injectate divided by the area under the curve for the venous concentration of 125I, was, on average, 8.5 ml min-1 100 g-1 forearm. Assuming [125I]albumin is a partially permeable tracer, a correction for extraction of albumin was performed. This gave extraction fractions of 0.107 +/- 0.015 (mean +/- SEM) for [14C]inulin and 0.377 +/- 0.033 for [51Cr]EDTA, respectively. The capillary permeability surface area product per 100 g tissue (CDC) was for [14C]inulin 0.90 +/- 0.19, and for [51Cr]EDTA 3.31 +/- 0.38 ml min-1 100 g-1 forearm. The average of the ratios of the CDC values of [51Cr]EDTA to those of [14C]inulin, 4.0 +/- 0.5, is significantly higher than the corresponding ratio between the measured free diffusion coefficients in water at 37 degrees C, 3.07 +/- 0.002 (N = 36 and 17, respectively). This indicates that there is some degree of restriction for [14C]inulin (MW 5200) relative to [51Cr]EDTA (MW 340.2) and it points to an 'equivalent pore radius estimate' of about 160 A in human muscle capillaries.

Adult↗
PubMed1985

Variations in capillary permeability from apex and crypt in the villus of the ileo-jejunum.

The permeability of fenestrated capillaries in an organ is believed to be homogeneous. However, the permeability of fenestrated capillaries in different organs and to various exogenous tracers varies from a complete restriction, as found in the eye (Pino and Essner 1980, 1981; Pino 1985a) to the freely permeable peritubular capillaries of the kidney (Venkatachalam and Karnovsky 1972). In the present report we demonstrate that within any single intestinal villus from the ileo-jejunum of the rat, the permeability of fenestrated capillaries is not uniform. Exogenous hemoglobin (Einstein-Stokes radius [ESR] = 3.2 nm) exists all capillaries at any villar level in less than 5 min. In contrast, all villar capillaries restrict catalase (ESR = 5.2 nm) at 5 min, but by 60 min the tracer is present extravascularly in crypt and lower villar regions. Apical capillaries are slightly permeable to catalase at 2 h, but the bulk of the tracer remains in the lumina. The particulate tracer ferritin (ESR = 6.1 nm) is restricted 3-10 times more by apical capillaries than basal ones and is found in increasing concentration extravascularly at lower villar and crypt levels after 20 min. Following an 18-h circulation, a second dosage of ferritin is restricted by the endothelium at all villar levels. Immunocytochemical localizations of the plasma proteins albumin (ESR = 3.5 nm) and IgG (ESR = 5.5 nm) revealed an apparent lack of restriction at all villar levels. These results demonstrate that apical villar capillaries in the ileo-jejunum are more restrictive to exogenous molecules with ESR greater than or equal to 5.2 nm. Also, the passage of tracer molecules out of an endothelium alters the subsequent permeability of that vessel.

Animals↗
PubMed1990

Capillary permeability factor secreted by malignant brain tumor. Role in peritumoral brain edema and possible mechanism for anti-edema effect of glucocorticoids.

Conditioned media from two human malignant gliomas, C6 rat glioma, Walker 256 carcinosarcoma, and normal human glia were concentrated 50-fold to create a culture supernatant (SUP-C). The effect of SUP-C on rat brain capillary permeability was investigated by measuring the entry of 14C-aminoisobutyric acid (14C-AIB) by means of quantitative autoradiography. The SUP-C contained proteins with a molecular weight of 10 kD or greater. The SUP-C from all tumor cells markedly increased brain capillary permeability, indicating the presence of a permeability factor, whereas that from normal glial cells did not. Glioma cells produced more factor after incubation for 20 hours than 4 hours. The activity of capillary permeability factor in the SUP-C was inhibited by pretreatment of animals with BW755C (lipoxygenase inhibitor), but not with indomethacin (cyclo-oxygenase inhibitor). Pretreatment of animals with dexamethasone prior to intracerebral infusion of tumor SUP-C significantly reduced the factor-induced increase in capillary permeability. On the other hand, coincubating glioma cells with dexamethasone produced SUP-C with a permeability activity that was about one and a half times greater than that without dexamethasone. These results indicate that glucocorticoids produce their anti-edema effects by directly acting on capillary endothelial cells, possibly through the inhibition of phospholipase A2 activity, resulting in a decrease of lipoxygenase rather than cyclo-oxygenase products. The production of capillary permeability factor by tumor cells was not inhibited, but rather enhanced, by administration of glucocorticoids.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed2000

Purification and characterization of a growth factor-like which increases capillary permeability from Vipera lebetina venom.

We have investigated the effect of Vipera lebetina venom on capillary permeability and isolated an increasing capillary permeability protein (ICPP) which is devoid of arginine ester hydrolase and phospholipase A2 activities. This protein was purified with a yield of about 0.2% by fast protein liquid chromatography (FPLC) using successively Superose 12, Mono Q, and Mono S columns and by high-pressure liquid chromatography (HPLC) on a C8 reverse-phase column. The purified protein migrated on SDS-PAGE as a band of about 27 kDa under nonreducing conditions and as a band of about 16 kDa under reducing conditions. Chromatography on a C8 column of reduced and alkylated protein yielded a single peak suggesting that this protein is homodimeric. This protein was refractory to Edman degradation chemistry. We used successfully a chemical unblocking involving the incubation of the protein with HCl in anhydrous methanol. The N-terminal amino acid sequence clearly shows considerable similarity to that of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF).

Amino Acid Sequence↗
PubMed1977

Nature of histamine receptors concerned in capillary permeability.

1 Histamine and 2-methyl-histamine (H1-receptor agonist) caused dose-dependent increases in capillary permeability in albino mice, but 4-methyl-histamine (H2-receptor agonist) caused no significant increase. 2 Mepyramine (H1-receptor antagonist) blocked the histamine-induced increase in capillary permeability whereas burimamide (H2-receptor antagonist) produced no significant blockade of the histamine-response. 3 Combined mepyramine and burimamide pretreatment did not give any significantly greater protection than mepyramine alone. 4 The results indicate involvement of the H1-receptors in histamine-induced increase in capillary permeability.

Animals↗
PubMed1996

Contrast-enhanced MR imaging assessment of tumor capillary permeability: effect of irradiation on delivery of chemotherapy.

PURPOSE: To assess the effect of x rays on tumor capillary permeability with macromolecular contrast medium (MMCM)-enhanced magnetic resonance (MR) imaging. MATERIALS AND METHODS: One of paired R3230 mammary adenocarcinomas implanted in the flanks of 48 Fischer rats was treated with a single 5- or 15-Gy dose of x rays. After 1 or 3 days, MR imaging in 30 rats was performed unenhanced and enhanced with albumin-(gadolinium diethylenetriaminepentaacetic acid)30 (0.02 mmol gadolinium per kilogram body weight). Signal intensity enhancement was analyzed to estimate fractional blood volume and permeability-surface area product (PS). In 18 irradiated rats, 2.5 mg/kg cisplatin was injected intravenously, and fractional tumor platinum concentrations were measured spectrometrically. RESULTS: MR imaging showed highest capillary permeability 1 day after 15 Gy (PS 110% above control [P<.001]); PS was elevated 57% 1 day after 5 Gy and 63% 3 days after 15 Gy (P<.05). The largest mean tumor platinum fraction occurred 1 day after 15 Gy: 48% versus 20% (control)(P<.05). CONCLUSION: Transient irradiation-induced increase in tumor capillary permeability to cisplatin can be quantified with MMCM-enhanced MR imaging.

Albumins↗
PubMed1996

Effects of inflation volume during lung preservation on pulmonary capillary permeability.

UNLABELLED: The degree of lung allograft inflation during harvest and storage may affect posttransplantation function. High volume ventilation causes pulmonary vascular injury and increased pulmonary capillary permeability. However, the effect of lung inflation on pulmonary capillary permeability after hypothermic flush and storage is unknown. The current study was designed to examine the effects of hyperinflation and hypoinflation during preservation on pulmonary vascular permeability. METHODS: An isolated, ex vivo rabbit lung gravimetric model without the confounding effects of reperfusion was used to determine post pulmonary capillary filtration coefficients (Kf). New Zealand White rabbits (2.75 to 3.15 kg) were intubated and lungs ventilated with room air (tidal volume 25 ml). After sternotomy and heparinization, the pulmonary artery was flushed with low potassium dextran-1% glucose solution (200 ml). The heart-lung block was then excised. Two studies were conducted. For measurement of changes in airway pressure and lung volume during preservation, lungs were inflated to one of four storage volumes (12, 25, 40, 55 ml) with room air, 100% O2, or 100% N2 and stored at 10 degrees C in a sealed container filled with saline solution. During preservation, lung volume and airway pressure were measured at 3, 6, 12 and 24 hours. In the Kf study, lungs were inflated with 100% O2, 50% O2 (with 50% N2), or room air and preserved. After 24 hours of preservation at 10 degrees C, the heart-lung block was suspended from a strain-gauge force transducer and the lungs were ventilated with room air. The pulmonary artery was connected to a reservoir of hetastarch solution (6% hetastarch with 0.9% saline solution). Lung weight gain, airway pressure, pulmonary artery pressure, and left atrial pressure were measured continuously. After a brief flush with hetastarch solution, the reservoir was then elevated to achieve 1.0 to 1.5 mm Hg increments in pulmonary artery pressure. RESULTS: The slope of subsequent steady-state lung weight gain was used to determine the Kf. The current study demonstrated the following: (1) changes in lung volume and airway pressure during storage increased with intraalveolar O2 concentration, (2) irrespective of inflation, fraction of inspired oxygen, hyperinflation during lung preservation increased the Kf in a volume-dependent fashion; (3) Kf was increased in lungs stored hypoinflated with room air; and (4) at any inflation volume, the Kf was significantly increased with 100% O2 inflation after 24 hours of preservation. CONCLUSION: These results suggest that storage at high lung volume or high inspired oxygen fraction increases pulmonary capillary permeability.

Animals↗